Researchers in Singapore have devised a new method for controlling pigmentation in 3D bioprinted human skin. The research could lead to more lifelike fabricated skin for grafting, toxicology, and chemical testing.

New bioprinting research could lead to printed skin with lifelike pigmentation

At present, 3D bioprinting represents a highly effective (if still exploratory) way of engineering skin constructs for various tasks: skin repair and grafting, toxicology, and chemical testing, to name but a few.

However, printed skin isn’t perfect. It generally lacks complex features like pigmentation, sweat glands, or hair follicles, and therefore doesn’t look or behave quite like the real thing. That’s not a problem for all applications, but for uses like skin grafts on humans, it can be the difference between a happy patient and a disappointed one.

In a research project that could be big news for skin bioprinting, researchers from A*STAR's Singapore Institute of Manufacturing Technology (SIMTech) and the Singapore Centre for 3D Printing (SC3DP) at Nanyang Technological University have used 3D bioprinting to control the distribution of melanin-producing skin cells (melanocytes) on a biomimetic tissue substrate. The result is digitally fabricated skin that is more human-like than ever.

“3D bioprinting is an excellent platform for the precise deposition of biomaterials and living cells to make biomimetic skin in large volumes with great repeatability,” explains lead author Wei Long Ng. “However, non-uniform skin pigmentation is often seen, and this remains a huge challenge to be solved. Our aim with this project was to use this method to demonstrate the feasibility of making 3D in vitro pigmented human skin constructs with uniform skin pigmentation.”

So how does it all work? Just how did these researchers manage to create lifelike skin pigmentation using a 3D bioprinter? The secret, the researchers say, is in using no fewer than three different types of skin cells—keratinocytes, melanocytes, and fibroblasts—while employing a “drop on demand” approach to bioprinting that consists of two distinct stages.

Researchers from Nanyang Technological University contributed to the research

The two steps in this two-step approach to bioprinting are: fabricating hierarchical porous collagen-based structures that closely resemble the skin's dermal region, and depositing epidermal cells such as keratinocytes and melanocytes at pre-defined positions on top of those skin constructs.

Together, these two stages result in 3D in vitro pigmented human skin constructs, and the researchers found that they could distribute live cells in a much more precise way using this bioprinting approach. “When we compared the 3D bioprinted skin constructs to those made using a manual casting method, we found two distinct differences between the two fabrication approaches,” says Wei Long.

The first of these differences was the cell distribution on top of the dermal regions, and the second was the microstructures within the dermal regions. Wei Long added that the two-step bioprinting approach “enables the standardized distribution of printed cells in a highly controlled way, as compared to the manual casting approach.”

There are other advantages to the 3D bioprinting process too. According to the Singapore researchers, the two-stage procedure allows scientists to manipulate pore sizes within the 3D collagen-fibroblast matrices, letting them build the kind of hierarchical porous structures seen in normal skin. The researchers say this is much harder to achieve using a manual casting approach.

Ultimately, because of the ease with which it can produce complex skin structures, the uses for this bioprinting development could be manifold. Being able to 3D print skin grafts with correct pigmentation is a huge achievement, since it could allow surgeons to repair wounds with a high level of visual subtlety. But the new method could also be used to make skin structures for drug testing and cell biology research, amongst other things.

The study has been documented in a research paper, “3D bioprinting of pigmented human skin constructs,” which has been published in the journal Biofabrication. Its other authors were Jovina Tan Zhi Qi, Wai Yee Yeong, and May Win Naing.